The goal of this project is to isolate and sequence fragments of genomic DNA that encode neurotransmitter receptors or are in regions associated with neurologic diseases. Such sequences can be used as a starting point to determine the structure and regulation of these neurotransmitters and aid in the precise localization and identification of the lesion responsible for the genetic disease. In order to accomplish these goals, we have continued to develop new laboratory procedures and test new automation to rapidly increase the rate at which we are able to sequence and analyse genomic DNA. We have continued the analysis of three cosmids we sequenced from chromosome 4 that were derived from the 2.2 million base region thought to contain the Huntington's disease gene. We have determined the complete structure of one of the genes contained in this region. We have also identified 72 polymorphisms in this sequence which can be used to further refine the location of the Huntington's disease gene. The sequence of a Drosophila octopamine receptor gene has been nearly completed and the promoter for that gene isolated. We have also, in a collaborative effort, sequenced portions of the gene responsible for neurofibromatosis. In addition we have nearly completed sequencing of the smallpox variola virus.